Fecal transplants cure diarrhea, modulate testosterone levels

Nutella was not used as a placebo control.

From some perspectives, we humans aren't really so much individuals as we are walking ecosystems—our bodies carry more bacterial cells—with their own genomes and agendas—than the total count of human cells we're composed of. Bacteria cover our skin, get to our food before we have the chance to absorb it, and in many cases stay helpfully out of the way of the immune system.

Given all that, it shouldn't be a surprise that we're finding that bacteria can have significant effects on the human body in ways that go well beyond causing an infection. Two articles that appeared this week drive that home. In one, doctors cured a recurring, diarrhea-causing infection simply by transplanting gut bacteria from a healthy individual. And in the second, the bacterial transplants altered the progression of type 1 (autoimmune) diabetes in mice—by altering the animal's testosterone levels.

Fighting bacteria with bacteria

Clostridium difficile, or C. diff, is a bacteria that tends to cause extended bouts of diarrhea. In about 20 percent of the cases that end up under a doctor's care, it will get into the digestive system and refuse to come back out, creating recurring bouts of illness that don't respond to most antibiotics. At that point, the standard of care is an intensive course of vancomycin, which only works in about 60 percent of patients. With each further recurrence, the rate of success goes down even further.

Anecdotal evidence and case reports had suggested that the problem wasn't so much the presence of C. diff as the fact that it had grown out of balance with the rest of the gut's bacterial ecosystem. To get the gut back into balance, fecal transplants had been tried and, anecdotally at least, they worked. So some doctors in the Netherlands decided to do a clinical trial, comparing a fecal transplant to standard care with vancomycin. The trial was what the researchers called "open label," meaning that people were aware they were having a feeding tube stuffed down their nose to deliver someone else's poop into their body. (A Twitter pundit suggested a Nutella infusion might make for a good placebo control.)

A few dozen healthy volunteers were screened for a huge panel of infectious diseases, and those who came through clean were asked to rush their bodies' first deliveries of the day to the hospital, where it was mixed with saline and had the particulates removed. The results then went into the gastro-nasal tube, given to patients after their original gut flora had been cleared out by a "bowel lavage."

The authors had originally planned to get 40 patients for each group, but the fecal transplants were so successful, they stopped the trial after only 16 patients had received a transplant. Of these, 13 (80 percent) were cured after a single transplant. Two of the remaining three were cured after their second, bringing the success rate up to over 90 percent. In contrast, the success rate of vancomycin treatments was down around 30 percent.

The biggest problem? Enrolling patients. Most people who agreed to participate in the trial only did so after conventional treatments failed several times, "reflecting the reluctance of patients and physicians to choose donor-feces infusion at an early stage."

Bacteria, sex, and immunity

It's easy to view this as a demonstration of the hygiene hypothesis, which posits that all sorts of health issues are linked to exposure to a variety of infectious agents, which the immune system then learns to live in harmony with. But a second paper appeared this week that cautioned against viewing things as being quite that simple.

The paper focused on the progression of type 1 diabetes, which is the product of an autoimmune attack on the insulin-producing cells. There's a special strain of mice, called NOD (for non-obese diabetic) that are prone to developing this disorder. The mice show properties that are very much like the human version of the disease: it's genetically complex, the progression is influenced by environmental factors, and it strikes females more severely than males.

And, unexpectedly, it's influenced by gut bacteria. There was some hint of this, given that other researchers had shown that a systematic exposure to bacterial proteins was able to suppress the development of the disease. But the authors found an unexpected effect when they tested how the disorder progressed in mice raised in germ-free conditions. Rather than accelerating the development of symptoms in all mice, the germ-free conditions accelerated the progression in males, making them (at least in this assay) indistinguishable from females.

So the researchers tried an experiment: they took germ-free NOD mice and did a fecal transplant from adult male animals (mice are naturally coprophagic, so the mice took a lot less convincing than did the humans). When female NOD mice received gut bacteria from males, it actually slowed the disease progression down. The apparent sex difference in autoimmune function was mediated in part by gut bacteria.

Your first thought might be that testosterone in males could create a different environment in the gut, causing it to host a different diversity of species. It's a reasonable guess, but it's wrong. Instead, the researchers found that the transplant of gut bacteria caused a surge in testosterone production by females that lasted for up to 14 weeks. This had no effect on the female's fertility, but it did clearly alter immune function. If the authors injected these mice with a testosterone inhibitor, the diabetes protection went away.

All of which indicates that the other intuitive idea—that gut bacteria influence immune function by interacting directly with immune cells—also can't be right, or at least can't be everything. Clearly, the production of testosterone, by whatever cells may be producing it, plays a key role.

Although the papers argue against some of the simpler views of human health—bacteria are all bad, or not having exposure to pathogens means an overactive immune system—they both argue that viewing our bodies as a complex ecosystem can help provide insight into human health.

Went back and forth on whether or not to go there, ultimately Eric and I couldn't resist. But just to be clear I think this is really fascinating and serious science, so hopefully the little joke doesn't overshadow that!

I'm fascinated with the role of our gut bacteria in our lives, we've only scratched the surface of understanding IMHO.

Wow, that's crazy, especially the fecal transplant (fucking EW) why didn't they just take a culture of bacteria present in the stomachs of healthy individuals, and grow those bacteria on a pea tree dish?

I was prescribed clindamycin antibiotic by a dentist about 6 years ago. Ever since then my GI system has been on the fritz. Theory is bacterial imbalance. Some have been killed out completely and others have moved into the empty habitat and overgrown. I've had tests done for c.Diff twice and both came back negative, even though I'm fairly certain that's the problem. I've been treated with vancomycin which worked only for as long as I took it. Tests for this are imperfect. Doctors know very little about it. It's all on the cutting edge of research at the moment.

I've self treated with a GF diet and off the shelf probiotics for years. Just two weeks ago things came to a head with mild to moderate abdominal pains. Imaging (just yesterday!) showed nothing wrong.

I had assumed by transplanting they used some turkey baster type device inserted into the anus of another specimen to transplant the fecal matter.

I was wrong.

That method (well not exactly that, but right idea) has been used in other trials of the concept. Personally while it still triggers the childish "ew weird" reaction it seems a lot less so than going up a tube in your nose.

I've self treated with a GF diet and off the shelf probiotics for years. Just two weeks ago things came to a head with mild to moderate abdominal pains. Imaging (just yesterday!) showed nothing wrong.

Curious why a GF diet? Does that really seem to work for you? Are you label reading down to PPM or just avoiding the big sources? It's a lot easier to go GF these days, but still I pretty big PITA commitment (I can personally attest to that).

I've self treated with a GF diet and off the shelf probiotics for years. Just two weeks ago things came to a head with mild to moderate abdominal pains. Imaging (just yesterday!) showed nothing wrong.

Curious why a GF diet? Does that really seem to work for you? Are you label reading down to PPM or just avoiding the big sources? It's a lot easier to go GF these days, but still I pretty big PITA commitment (I can personally attest to that).

It seems to help. Actually it "cured" me completely when I originally discovered GF.... for a about a week. Then the symptoms came back somewhat. That's the thing. You push against life (bacteria), and it tends to push back. Same reason why our antibiotics are becoming less effective.

Anyhow, the tube through nose is weird. I've heard of colonoscopy apparatus being used to deposit fecal matter into intestines.

...so, "The human Centipede" was a public education program in disguise...

ughhh

as an aside, the concept of our metabolism and our gut fauna/flora existing as an ecosystem is exemplified by a study where they showed that bacterial populations change throughout pregnancy in human female guts (http://www.ncbi.nlm.nih.gov/pubmed/22863002), and that transplanting feces of pregnant women (but not non-pregnant women) into immune deficient mice causes the equivalent of metabolic syndrome in the mice. Apart from what it teaches us about our intricate relationship with our gut biota it teaches us a second lesson. Never eat the poo of pregnant women.

Wow, that's crazy, especially the fecal transplant (fucking EW) why didn't they just take a culture of bacteria present in the stomachs of healthy individuals, and grow those bacteria on a pea tree dish?

From the article it sounds like they wanted the correct ratio. I imagine that growing in a dish would warp that some what.

I'd agree with OsirisDean. Using that tagline on the image was a masterpiece. I wonder how UPS feels about it?

While hilarious, Aurich missed the perfect opportunity to use the 'correct' medical term:

A transpoosion.

(Seriously, this appears to be a fantastic advance. I've been following this for some time. Now all we ideally need to do is work on a less "yucky" delivery mechanism for delivering a healthy population of gut bacteria.)

"A fresh perspective on autism research with the developing "Bacterial Theory" of autism. The fastest-growing developmental disorder in the industrialized world, autism has increased an astounding 600 per cent over the last 20 years. Science cannot say why. Some say it's triggered by environmental factors and point to another intriguing statistic: 70 per cent of kids with autism also have severe gastrointestinal symptoms. Could autism actually begin in the gut? The Autism Enigma looks at the progress of an international group of scientists who are studying the gut's amazingly diverse and powerful microbial ecosystem for clues to the baffling disorder."

Wow, that's crazy, especially the fecal transplant (fucking EW) why didn't they just take a culture of bacteria present in the stomachs of healthy individuals, and grow those bacteria on a pea tree dish?

I imagine it's probably to maintain the same population ratios present in the healthy guts, since it's not well-understood which colonies (if not all of them) are necessary - and as the beginning of the article suggests, the relative balance is important as well. Removing the entire population from their preferred environment (the human gut) could favor some species over others, relative to getting it from a more, erm, "fresh" source.

Went back and forth on whether or not to go there, ultimately Eric and I couldn't resist. But just to be clear I think this is really fascinating and serious science, so hopefully the little joke doesn't overshadow that!

I'm fascinated with the role of our gut bacteria in our lives, we've only scratched the surface of understanding IMHO.

I'm fascinated by the concept of us actually not being a single organism, but the product of a symbiotic relationship between several: what we typically consider our own cells, our gut flora, and even our mitochondria. It's really amazing to think about.

Wow, that's crazy, especially the fecal transplant (fucking EW) why didn't they just take a culture of bacteria present in the stomachs of healthy individuals, and grow those bacteria on a pea tree dish?

I hope you were joking with your "pea tree dish" otherwise Julius Petri might come back from the grave to haunt you.

for DilbertI have read of success treating C diff with fecal enema which would seem to decrease (only slightly) the eww factor. There is also a group in Britain trying to get approval for purified bacterial products to administer in a capsule form.

What a interesting article and I have curious question which I have no idea if it is related or not. What about people who suffer from irritable bowl syndrome? Could this research help out with that problem?

"A fresh perspective on autism research with the developing "Bacterial Theory" of autism. The fastest-growing developmental disorder in the industrialized world, autism has increased an astounding 600 per cent over the last 20 years. Science cannot say why. Some say it's triggered by environmental factors and point to another intriguing statistic: 70 per cent of kids with autism also have severe gastrointestinal symptoms. Could autism actually begin in the gut? The Autism Enigma looks at the progress of an international group of scientists who are studying the gut's amazingly diverse and powerful microbial ecosystem for clues to the baffling disorder."

Except that's almost certainly wrong. We've gotten a good grip on the genetics that are behind many cases of both sporadic and inherited autism, and they consistently affect proteins that control brain development. If this model were right, we'd see more genes with a significant immune influence. We don't.

I don’t have this same set of symptoms, but I’ve suffered from frequent bloating and abdominal pains for a few years and modern medicine has no idea what’s going on. I’ve given lots of samples (of various things), gotten ultrasounds, had a camera stuck down my throat, taken expensive pills, cycled through giving up certain foods/drinks for a while… nothing. I’d probably do this if they figured out it worked for my symptoms.

Since that option didn’t exist, I ended up going to an acupuncturist out of desperation. Between that and the herbal brews the ‘doctor’ gave me, the frequency of my symptoms decreased by about 90%. I don’t think it was all mental, because I certainly don’t believe that I have a qi block causing all my problems. Maybe it was the herbs. (I should’ve tried just the herbs, but this guy’s English was worse than my paltry Mandarin, so I just let him do his thing.) Anyway, I recommend trying it if real doctors haven’t been able to help. Clearly this is one aspect of medicine that isn’t very well developed yet.

"A fresh perspective on autism research with the developing "Bacterial Theory" of autism. The fastest-growing developmental disorder in the industrialized world, autism has increased an astounding 600 per cent over the last 20 years. Science cannot say why. Some say it's triggered by environmental factors and point to another intriguing statistic: 70 per cent of kids with autism also have severe gastrointestinal symptoms. Could autism actually begin in the gut? The Autism Enigma looks at the progress of an international group of scientists who are studying the gut's amazingly diverse and powerful microbial ecosystem for clues to the baffling disorder."

Except that's almost certainly wrong. We've gotten a good grip on the genetics that are behind many cases of both sporadic and inherited autism, and they consistently affect proteins that control brain development. If this model were right, we'd see more genes with a significant immune influence. We don't.

Cool, I was under the impression that we don't know a fucking thing about Autism causes. Apparently Autism is neither an enigma nor baffling. How could the scientists in the CBC study be so clueless?

As someone that's passably familiar with the current research on the human microbiome, I find this very exciting. The article eludes to the fact that bacterial links to the immune system have been found going back to 2005 and further. The popularity of Cesarean births leads to some children having immune system irregularities, since it is known that the vaginal canal transfers a "starter" colony of gut bacteria to the child at the time of birth. Perhaps future studies will concentrate on allergies or skin problems such as eczema. After looking into these things, it seems that most doctors take the "Hiroshima approach" to correcting bacterial imbalance in the body. Hopefully as we learn more about how our passengers work, they will be less inclined to nuke them all.

On a side note, the realities of the microbiome make the idea of human hosted nanotechnology seem kind of dumb. Why create weird microrobots from scratch when you already have a whole ecosystem of organisms to work with that are already there helping out? We already know plenty about bacterial genetic modification.